The proposed Mental Retardation and Developmental Disabilities Research Center (MRDDRC) was established in 1990 and renewed in 1995 and 1999. It represents the collaboration of the Children's Hospital of Philadelphia and the University of Pennsylvania (Penn). In this renewal application, funds are requested to support five core facilities and New Program Development projects. The cores are: (A) Administrative Core, which provides overall management of the MRDDRC. It administers all educational programs, lecture series, and the New Program Development projects. It also oversees the proposed Mid-Atlantic Research Consortium, a new venture that would encourage more joint research at the MRDDRCs at Penn, Johns Hopkins, and Children's National Medical Center. (B) Biostatistics and Bioinformatics, which provides consultation with regard to study design, statistical analysis, and database design. A new emphasis is bioinformatics, which is crucial to the interpretation of data culled from chip array analysis of DNA. (C) Molecular Genetics, which provides a centralized facility for DNA sequencing, fluorescent fragment analysis, mutation detection with cosmig contigs, screen of YAC libraries, quantitative PCR analysis, gene mapping, cell culture, etc. (D) Analytical Neurochemistry and Spectroscopy, which provides expert and support with regard to biochemical analyses. The core facilitates a wide spectrum of neurochemical analysis, from brain tissue to living cells in vitro to the intact organism. It combines mass spectrometric analysis of stable isotopes, HPLC of biogenic amines and amino acids, positron emission tomography (PET) services and fluorescent assays in live cells. A new component is the proposed Proteomics Subcore that facilitates characterization of proteins of neurochemical interest. (E) Cellular Neuroscience, which provides support and advice with regard to confocal microscopy, cytoarchitectural analysis, and cell culture. A new component is the availability of techniques for optically imaging circuit function in slice preparations using voltage sensitive dyes. Finally, the core proposes to provide users with expertise for the development and preservation of mouse models (transgenic and knock-outs). These units service more than 96 NIH -funded projects with an aggregate annual value of more than $12 million (greater than $1.5 million from NICHD). The Center includes more than 60 Penn faculty members representing 15 departments at the School of Medicine, School of Veterinary Medicine, The School of Nursing, the Wistar Institute, and the College of Arts and Sciences.